CA2484345C - Folate-targeted imaging agents - Google Patents
Folate-targeted imaging agents Download PDFInfo
- Publication number
- CA2484345C CA2484345C CA2484345A CA2484345A CA2484345C CA 2484345 C CA2484345 C CA 2484345C CA 2484345 A CA2484345 A CA 2484345A CA 2484345 A CA2484345 A CA 2484345A CA 2484345 C CA2484345 C CA 2484345C
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- CA
- Canada
- Prior art keywords
- compound
- deazafolates
- dideazafolates
- radionuclide
- folate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
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Landscapes
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- Investigating Or Analysing Biological Materials (AREA)
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
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| DK2258401T3 (da) | 2002-05-06 | 2014-10-13 | Endocyte Inc | Folat-receptor targetede billeddannelsesmidler |
| DE60326833D1 (de) * | 2002-05-15 | 2009-05-07 | Endocyte Inc | Vitamin-mitomycin-konjugate |
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| JP4680185B2 (ja) | 2003-05-30 | 2011-05-11 | パーデュー・リサーチ・ファウンデーション | アテローム性動脈硬化症の診断法 |
| EP1789391B1 (en) | 2004-07-23 | 2017-06-28 | Endocyte, Inc. | Bivalent linkers and conjugates thereof |
| US7977500B2 (en) * | 2004-11-10 | 2011-07-12 | University Of South Florida | Platinum complexes for targeted drug delivery |
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| CN101646639A (zh) | 2007-04-11 | 2010-02-10 | 默克阿泼洛发股份公司 | 18f-标记的叶酸 |
| KR101605426B1 (ko) * | 2007-04-11 | 2016-03-22 | 메르크 앤드 씨에 | 진단 이미징 및 방사선치료에 사용하기 위한 폴레이트-컨쥬게이트 및 대응하는 금속-킬레이트 착물 |
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| CA2690943A1 (en) | 2007-06-25 | 2008-12-31 | Endocyte, Inc. | Conjugates containing hydrophilic spacer linkers |
| US9877965B2 (en) | 2007-06-25 | 2018-01-30 | Endocyte, Inc. | Vitamin receptor drug delivery conjugates for treating inflammation |
| SI2187965T1 (sl) | 2007-08-17 | 2020-03-31 | Purdue Research Foundation Office Of Technology Commercialization | Konjugati vezalca ligand-veznika PSMA in metode za uporabo |
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| US11298113B2 (en) | 2008-10-01 | 2022-04-12 | Covidien Lp | Device for needle biopsy with integrated needle protection |
| US9186128B2 (en) | 2008-10-01 | 2015-11-17 | Covidien Lp | Needle biopsy device |
| US8968210B2 (en) | 2008-10-01 | 2015-03-03 | Covidien LLP | Device for needle biopsy with integrated needle protection |
| US8426398B2 (en) | 2009-01-13 | 2013-04-23 | Emory University | Conjugates of noscapine and folic acid and their use in treating cancer |
| WO2010101951A1 (en) | 2009-03-02 | 2010-09-10 | Alnylam Pharmaceuticals, Inc. | Nucleic acid chemical modifications |
| CA2754492A1 (en) * | 2009-03-05 | 2010-09-10 | Purdue Research Foundation | Method for early imaging of atherosclerosis |
| US9951324B2 (en) | 2010-02-25 | 2018-04-24 | Purdue Research Foundation | PSMA binding ligand-linker conjugates and methods for using |
| HRP20151294T1 (hr) | 2010-04-05 | 2016-03-11 | Prognosys Biosciences, Inc. | Biološka testiranja sa prostornim kodiranjem |
| US10787701B2 (en) | 2010-04-05 | 2020-09-29 | Prognosys Biosciences, Inc. | Spatially encoded biological assays |
| US20190300945A1 (en) | 2010-04-05 | 2019-10-03 | Prognosys Biosciences, Inc. | Spatially Encoded Biological Assays |
| WO2011130716A2 (en) | 2010-04-16 | 2011-10-20 | Access Pharmaceuticals, Inc. | A nanostructures containing vitamin b12 for facilitated delivery of drugs across biological barriers |
| WO2011133868A2 (en) | 2010-04-22 | 2011-10-27 | Alnylam Pharmaceuticals, Inc. | Conformationally restricted dinucleotide monomers and oligonucleotides |
| WO2011133876A2 (en) | 2010-04-22 | 2011-10-27 | Alnylam Pharmaceuticals, Inc. | Oligonucleotides comprising acyclic and abasic nucleosides and analogs |
| CN103501821A (zh) | 2011-03-08 | 2014-01-08 | 艾克塞斯制药公司 | 用于递送活性剂穿过生物膜的靶向纳米载体系统 |
| GB201106254D0 (en) | 2011-04-13 | 2011-05-25 | Frisen Jonas | Method and product |
| KR102036199B1 (ko) | 2011-08-17 | 2019-10-24 | 메르크 앤드 씨에 | 알부민-결합 개체들의 폴레이트 공액체들 |
| US9884123B2 (en) | 2012-01-03 | 2018-02-06 | Invictus Oncology Pvt. Ltd. | Ligand-targeted molecules and methods thereof |
| US10080805B2 (en) | 2012-02-24 | 2018-09-25 | Purdue Research Foundation | Cholecystokinin B receptor targeting for imaging and therapy |
| US9629918B2 (en) | 2012-02-29 | 2017-04-25 | Purdue Research Foundation | Folate receptor alpha binding ligands |
| US20140080175A1 (en) | 2012-03-29 | 2014-03-20 | Endocyte, Inc. | Processes for preparing tubulysin derivatives and conjugates thereof |
| US20150174273A1 (en) * | 2012-07-25 | 2015-06-25 | Emory University | Imaging and therapeutic methods for treating parathyroid tumors |
| IN2015DN04147A (cg-RX-API-DMAC7.html) | 2012-10-16 | 2015-10-16 | Endocyte Inc | |
| EP2909337B1 (en) | 2012-10-17 | 2019-01-09 | Spatial Transcriptomics AB | Methods and product for optimising localised or spatial detection of gene expression in a tissue sample |
| KR101551232B1 (ko) | 2012-10-26 | 2015-09-10 | 한국원자력연구원 | N3s1형의 새로운 킬레이터가 접합된 폴레이트 유도체, 이의 제조방법 및 이를 유효성분으로 함유하는 암 진단 또는 치료용 조성물 |
| KR102318999B1 (ko) | 2012-11-15 | 2021-10-29 | 엔도사이트, 인코포레이티드 | Psma 발현 세포에 의해 야기되는 질병을 치료하기 위한 컨쥬게이트 |
| WO2014150943A1 (en) * | 2013-03-15 | 2014-09-25 | Purdue Research Foundation | Asthma imaging and therapy |
| WO2014210223A1 (en) | 2013-06-25 | 2014-12-31 | Prognosys Biosciences, Inc. | Spatially encoded biological assays using a microfluidic device |
| GEP20237497B (en) | 2013-10-18 | 2023-04-10 | Deutsches Krebsforsch | Labeled inhibitors of prostate specific membrane antigen (psma), their use as imaging agents and pharmaceutical agents for the treatment of prostate cancer |
| US20160287731A1 (en) * | 2013-11-14 | 2016-10-06 | Endocyte, Inc. | Compounds for Positron Emission Tomography |
| EP3071971B1 (en) | 2013-11-19 | 2019-04-24 | Purdue Research Foundation | Patient selection method for inflammation |
| KR20160132496A (ko) | 2014-04-03 | 2016-11-18 | 인빅터스 온콜로지 피비티. 엘티디. | 초분자 조합 치료제 |
| EP3160514B1 (en) | 2014-06-27 | 2024-07-31 | Reiley Pharmaceuticals, Inc. | Conjugates derived from non-steroidal anti-inflammatory drugs and methods of use thereof in imaging |
| US20160166679A1 (en) * | 2014-12-12 | 2016-06-16 | Purdue Research Foundation | Method of treatment using folate conjugates and tyrosine kinase inhibitors |
| US20170369872A1 (en) | 2014-12-18 | 2017-12-28 | Alnylam Pharmaceuticals, Inc. | Reversir tm compounds |
| US10188759B2 (en) | 2015-01-07 | 2019-01-29 | Endocyte, Inc. | Conjugates for imaging |
| WO2016111834A1 (en) | 2015-01-09 | 2016-07-14 | Reiley Pharmaceuticals, Inc. | Cox-2-targeting, platinum-containing conjugates and their use in the treatment of tumors and cancers |
| ES2955488T3 (es) | 2015-04-10 | 2023-12-01 | Spatial Transcriptomics Ab | Análisis multiplex de especímenes biológicos de ácidos nucleicos espacialmente distinguidos |
| WO2017015109A1 (en) | 2015-07-17 | 2017-01-26 | Alnylam Pharmaceuticals, Inc. | Multi-targeted single entity conjugates |
| EP3334466B1 (en) | 2015-08-14 | 2020-05-13 | Endocyte, Inc. | Method of imaging with a chelating compound |
| KR102723865B1 (ko) | 2015-12-04 | 2024-10-29 | 10엑스 제노믹스, 인크. | 핵산 분석을 위한 방법 및 조성물 |
| JP2019515880A (ja) | 2016-03-16 | 2019-06-13 | エンドサイト・インコーポレイテッドEndocyte, Inc. | 炭酸無水酵素ix阻害剤抱合体およびその使用 |
| CA3017214A1 (en) * | 2016-03-16 | 2017-09-21 | Purdue Research Foundation | Carbonic anhydrase ix targeting agents and methods |
| US20170296679A1 (en) | 2016-04-18 | 2017-10-19 | Intuitive Surgical Operations, Inc. | Compositions of Near IR Closed Chain, Sulfo-Cyanine Dyes and Prostate Specific Membrane Antigen Ligands |
| ES3025461T3 (en) | 2017-08-22 | 2025-06-09 | Purdue Research Foundation | Fbsa-based therapeutic and radioimaging conjugates targeting carbonic anhydrase positive cancers |
| JP2021522193A (ja) | 2018-04-17 | 2021-08-30 | エンドサイト・インコーポレイテッドEndocyte, Inc. | 癌を治療する方法 |
| AU2019266207B2 (en) | 2018-05-07 | 2025-04-24 | Alnylam Pharmaceuticals, Inc. | Extrahepatic delivery |
| CA3114396A1 (en) | 2018-09-28 | 2020-04-02 | Alnylam Pharmaceuticals, Inc. | Transthyretin (ttr) irna compositions and methods of use thereof for treating or preventing ttr-associated ocular diseases |
| EP3969052A1 (en) | 2019-05-17 | 2022-03-23 | Alnylam Pharmaceuticals Inc. | Oral delivery of oligonucleotides |
| US12473265B2 (en) | 2019-05-20 | 2025-11-18 | Endocyte, Inc. | Methods for preparing PSMA conjugates |
| WO2021086982A2 (en) | 2019-10-28 | 2021-05-06 | Beckman Coulter, Inc. | Compounds for the identification of microbial classes and uses thereof |
| WO2021092145A1 (en) | 2019-11-06 | 2021-05-14 | Alnylam Pharmaceuticals, Inc. | Transthyretin (ttr) irna composition and methods of use thereof for treating or preventing ttr-associated ocular diseases |
| CA3160329A1 (en) | 2019-11-06 | 2021-05-14 | Alnylam Pharmaceuticals, Inc. | Extrahepatic delivery |
| US12399123B1 (en) | 2020-02-14 | 2025-08-26 | 10X Genomics, Inc. | Spatial targeting of analytes |
| US12281357B1 (en) | 2020-02-14 | 2025-04-22 | 10X Genomics, Inc. | In situ spatial barcoding |
| WO2021252499A1 (en) | 2020-06-08 | 2021-12-16 | 10X Genomics, Inc. | Methods of determining a surgical margin and methods of use thereof |
| US11981960B1 (en) | 2020-07-06 | 2024-05-14 | 10X Genomics, Inc. | Spatial analysis utilizing degradable hydrogels |
| US20230257745A1 (en) | 2020-07-10 | 2023-08-17 | Alnylam Pharmaceuticals, Inc. | Circular siRNAs |
| IL313194A (en) | 2020-10-30 | 2024-07-01 | Tod SPEER | Oligonucleotide-based treatments and their uses |
| US20240343746A1 (en) | 2020-12-31 | 2024-10-17 | Alnylam Pharmaceuticals, Inc. | Cyclic-disulfide modified phosphate based oligonucleotide prodrugs |
| US20240336914A1 (en) | 2020-12-31 | 2024-10-10 | Alnylam Pharmaceuticals, Inc. | 2'-modified nucleoside based oligonucleotide prodrugs |
| US20240165250A1 (en) * | 2021-01-08 | 2024-05-23 | Lycia Therapeutics, Inc. | Bifunctional Folate Receptor Binding Compounds |
| WO2022256503A1 (en) | 2021-06-03 | 2022-12-08 | 10X Genomics, Inc. | Methods, compositions, kits, and systems for enhancing analyte capture for spatial analysis |
| JP2024527584A (ja) | 2021-07-09 | 2024-07-25 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | CNS送達のためのBis-RNAi化合物 |
| CA3226269A1 (en) | 2021-07-14 | 2023-01-19 | Lycia Therapeutics, Inc. | Asgpr cell surface receptor binding compounds and conjugates |
| JP2024526890A (ja) | 2021-07-21 | 2024-07-19 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | 代謝障害関連標的遺伝子irna組成物およびその使用方法 |
| KR20240101590A9 (ko) | 2021-10-15 | 2025-12-10 | 알닐람 파마슈티칼스 인코포레이티드 | 간외 전달 irna 조성물 및 이를 이용하는 방법 |
| JP2025516680A (ja) | 2022-05-13 | 2025-05-30 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | 一本鎖ループオリゴヌクレオチド |
| JP2025522880A (ja) | 2022-06-30 | 2025-07-17 | アルナイラム ファーマシューティカルズ, インコーポレイテッド | 環状ジスルフィド修飾リン酸ベースのオリゴヌクレオチドプロドラッグ |
| WO2024073732A1 (en) | 2022-09-30 | 2024-04-04 | Alnylam Pharmaceuticals, Inc. | Modified double-stranded rna agents |
| WO2024238385A2 (en) | 2023-05-12 | 2024-11-21 | Alnylam Pharmaceuticals, Inc. | Single-stranded loop oligonucleotides |
| WO2025064660A2 (en) | 2023-09-21 | 2025-03-27 | Alnylam Pharmaceuticals, Inc. | Activin a receptor type 1c (acvr1c) irna compositions and methods of use thereof |
Family Cites Families (27)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US2816110A (en) * | 1956-11-23 | 1957-12-10 | Merck & Co Inc | Methods for the production of substituted pteridines |
| US5140104A (en) * | 1982-03-09 | 1992-08-18 | Cytogen Corporation | Amine derivatives of folic acid analogs |
| US5242679A (en) * | 1985-01-14 | 1993-09-07 | Neorx Corporation | Metal radionuclide labeled proteins for diagnosis and therapy |
| US5175343A (en) * | 1985-01-14 | 1992-12-29 | Neorx Corporation | Metal radionuclide labeled proteins for diagnosis and therapy |
| NZ217821A (en) | 1985-10-10 | 1989-07-27 | Biotech Australia Pty Ltd | Oral delivery system; complex of active agent and vitamin b12 or analogue thereof |
| GB8608335D0 (en) | 1986-04-04 | 1986-05-08 | Pfizer Ltd | Pharmaceutically acceptable salts |
| EP0273085A1 (en) | 1986-12-29 | 1988-07-06 | IntraCel Corporation | A method for internalizing nucleic acids into eukaryotic cells |
| US5053493A (en) * | 1987-04-02 | 1991-10-01 | Centocor Cardiovascular Imaging Partners, L.P. | Method for labeling antibodies with a metal ion |
| US5688488A (en) * | 1989-04-03 | 1997-11-18 | Purdue Research Foundation | Composition and method for tumor imaging |
| US7238340B1 (en) * | 1991-11-27 | 2007-07-03 | Cis Bio International | Monoamine, diamide, thiol-containing metal chelating agents |
| CA2101942C (en) | 1991-02-08 | 2001-01-30 | Richard T. Dean | Technetium-99m labeled polypeptides for imaging |
| US6335434B1 (en) * | 1998-06-16 | 2002-01-01 | Isis Pharmaceuticals, Inc., | Nucleosidic and non-nucleosidic folate conjugates |
| US5159079A (en) * | 1991-12-20 | 1992-10-27 | Eli Lilly And Company | 2-piperidones as intermediates for 5-deaza-10-oxo- and 5-deaza-10-thio-5,6,7,8-tetrahydrofolic acids |
| US6022966A (en) | 1993-11-22 | 2000-02-08 | Neorx Corporation | Pretargeting methods and compounds |
| DE4311022C2 (de) * | 1993-03-31 | 1996-07-11 | Diagnostikforschung Inst | Bifunktionelle chalkogenatom-unterbrochene Chelatbildner vom Typ S¶3¶N¶2¶ für radioaktive Isotope und deren Metallkomplexe, Verfahren zu ihrer Herstellung sowie diese enthaltende pharmazeutische Mittel |
| DE4310999C2 (de) * | 1993-03-31 | 1996-07-18 | Diagnostikforschung Inst | Bifunktionelle chalkogenatom-unterbrochene Chelatbildner vom Typ XN¶1¶S¶1¶X' für radioaktive Isotope und deren Metallkomplexe, Verfahren zu ihrer Herstellung sowie diese enthaltende pharmazeutische Mittel |
| DE4311021A1 (de) * | 1993-03-31 | 1994-10-27 | Diagnostikforschung Inst | Bifunktionelle Chelatbildner, deren Technetium- und Rhenium-Komplexe, Verfahren zu ihrer Herstellung und diese Verbindungen enthaltende radiopharmazeutische Mittel |
| DE4311023C2 (de) * | 1993-03-31 | 1996-05-02 | Diagnostikforschung Inst | Bifunktionelle chalkogenatom-unterbrochene Chelatbildner von Typ XN¶1¶S¶1¶O¶1¶ für radioaktive Isotope, deren Metallkomplexe, Verfahren zu ihrer Herstellung sowie diese enthaltende pharmazeutische Mittel |
| DE4425781A1 (de) * | 1994-07-14 | 1996-01-18 | Schering Ag | Technetium-Sulfonamid-Komplexe, deren Verwendung, diese enthaltende pharmazeutische Mittel, sowie Verfahren zur Herstellung der Komplexe und Mittel |
| US6083480A (en) * | 1997-05-01 | 2000-07-04 | Diatide, Inc. | Calcitonin receptor binding reagents |
| US6093382A (en) * | 1998-05-16 | 2000-07-25 | Bracco Research Usa Inc. | Metal complexes derivatized with folate for use in diagnostic and therapeutic applications |
| US6323313B1 (en) * | 1999-06-01 | 2001-11-27 | The University Of Washington | Annexin derivative with endogenous chelation sites |
| ES2518926T3 (es) * | 2000-06-02 | 2014-11-05 | Board Of Regents, The University Of Texas System | Conjugados de etilendicisteína y un análogo de glucosa |
| MXPA03010035A (es) | 2001-05-02 | 2004-06-30 | Purdue Research Foundation | Tratamiento y diagnostico de enfermedades mediadas por macrofagos. |
| DK2258401T3 (da) * | 2002-05-06 | 2014-10-13 | Endocyte Inc | Folat-receptor targetede billeddannelsesmidler |
| EP2517729A3 (en) * | 2003-01-27 | 2013-01-02 | Endocyte, Inc. | Vitamin receptor binding drug delivery conjugates |
| CA2524441C (en) * | 2003-05-06 | 2012-03-20 | Purdue Research Foundation | Treatment of lupus targeting the macrophages or the folate receptor |
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